Background: The Academy of Breastfeeding Medicine (ABM) revised the 2015 version of the substance use disorder (SUD) clinical protocol to review the evidence and provide updated literature-based recommendations related to breastfeeding in the setting of substance use and SUD treatments. Key Information: Decisions around breastfeeding are an important aspect of care during the peripartum period, and there are specific benefits and risks for substance-exposed mother-infant dyads. Recommendations: This protocol provides breastfeeding recommendations in the setting of nonprescribed opioid, stimulant, sedative-hypnotic, alcohol, nicotine, and cannabis use, and SUD treatments. Additionally, we offer guidance on the utility of toxicology testing in breastfeeding recommendations. Individual programs and institutions should establish consistent breastfeeding approaches that mitigate bias, facilitate consistency, and empower mothers with SUD. For specific breastfeeding recommendations, given the complexity of breastfeeding in mothers with SUD, individualized care plans should be created in partnership with the patient and multidisciplinary team with appropriate clinical support and follow-up. In general, breastfeeding is recommended among mothers who stop nonprescribed substance use by the time of delivery, and they should continue to receive ongoing postpartum care, such as lactation support and SUD treatment. Overall, enhancing breastfeeding education regarding substance use in pregnancy and lactation is essential to allow for patient-centered guidance.